NM_001039469.3:c.258_259dupGA

Variant names:

• chr11-63895601-A-AAG
• NM_001039469.3:c.258_259dupGA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001039469.3(MARK2):​c.258_259dupGA​(p.Thr87ArgfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MARK2 NM_001039469.3 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.01
• Publications: 0 publications found

Genes affected

MARK2 (HGNC:3332): (microtubule affinity regulating kinase 2) This gene encodes a member of the Par-1 family of serine/threonine protein kinases. The protein is an important regulator of cell polarity in epithelial and neuronal cells, and also controls the stability of microtubules through phosphorylation and inactivation of several microtubule-associating proteins. The protein localizes to cell membranes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-63895601-A-AAG is Pathogenic according to our data. Variant chr11-63895601-A-AAG is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3253644.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039469.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK2	NM_001039469.3	MANE Select	c.258_259dupGA	p.Thr87ArgfsTer4	frameshift	Exon 3 of 19	NP_001034558.2	Q7KZI7-1
	MARK2	NM_017490.4		c.159_160dupGA	p.Thr54ArgfsTer4	frameshift	Exon 3 of 18	NP_059672.2	Q7KZI7-14
	MARK2	NM_004954.5		c.258_259dupGA	p.Thr87ArgfsTer4	frameshift	Exon 3 of 17	NP_004945.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK2	ENST00000402010.8	TSL:1 MANE Select	c.258_259dupGA	p.Thr87ArgfsTer4	frameshift	Exon 3 of 19	ENSP00000385751.2	Q7KZI7-1
	MARK2	ENST00000513765.7	TSL:1	c.258_259dupGA	p.Thr87ArgfsTer4	frameshift	Exon 3 of 18	ENSP00000421075.3	Q7KZI7-8
	MARK2	ENST00000425897.3	TSL:1	c.258_259dupGA	p.Thr87ArgfsTer4	frameshift	Exon 3 of 17	ENSP00000415494.3	E7ETY4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Autism spectrum disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-63663073;